Rare genetic inflammatory skin disorders

Gene: NLRP1

Green List (high evidence)

Comment on mode of inheritance: As there are now 3 unrelated cases reported with biallelic NLRP1 variants and an inflammatory skin disorder, the MOI should be changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal.

Created: 24 Feb 2026, 2:52 p.m. | Last Modified: 24 Feb 2026, 2:52 p.m.

Panel Version: 4.16

3rd recessive case:
PMID: 36763876 Li et al., 2023
2 sibs with a homozygous p.Leu813Pro gain-of-function NLRP1 variant. Younger sister had generalized inflammatory nodules with keratotic plugs, clinically resembling multiple keratoacanthomas, while the older had manifestations of familial keratosis lichenoides chronica - both childhood onset. Parents were first cousins from North-Africa - both unaffected, heterozygous for the variant.

Created: 24 Feb 2026, 2:50 p.m. | Last Modified: 24 Feb 2026, 2:50 p.m.

Panel Version: 4.14

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Autoinflammation with arthritis and dyskeratosis, OMIM:617388; Palmoplantar carcinoma, multiple self-healing, OMIM:615225

Publications

• 36763876

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.

Created: 4 Dec 2024, 4:58 p.m. | Last Modified: 4 Dec 2024, 4:58 p.m.

Panel Version: 3.22

Comment on mode of inheritance: There is sufficient evidence available for the association of monoallelic NLRP1 variants to this panel with green rating. However, the evidence is not sufficient enough (two unrelated cases) for biallelic variants. Hence, the MOI should be changed to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' and this gene should be recommended for upgrade to green rating in the next GMS review.

Created: 2 Nov 2023, 2:48 p.m. | Last Modified: 2 Nov 2023, 2:48 p.m.

Panel Version: 3.5

There are five unrelated cases with monoallelic NLRP1 variants and two unrelated cases with biallelic NLRP1 variants reported with inflammatory skin conditions. Some of these variants are reported to be gain-of-function.

This gene has also been associated with relevant phenotypes in both OMIM and Gene2Phenotype.

Created: 2 Nov 2023, 2:45 p.m. | Last Modified: 2 Nov 2023, 2:46 p.m.

Panel Version: 3.4

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Autoinflammation with arthritis and dyskeratosis, OMIM:617388; Palmoplantar carcinoma, multiple self-healing, OMIM:615225

Publications

• 27662089
• 27965258
• 31873740

Mode of pathogenicity
Other

I don't know

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
AUTOINFLAMMATION WITH ARTHRITIS AND DYSKERATOSIS; AIADK

Publications

• 27965258

I don't know

This gene was part of a gene list collated by John McGrath, KCL and Veronica Kinsler, UCL, 17.Jun.2019 on behalf of the GMS Skin Specialist Test Group. Gene Symbol submitted:NLRP1; Suggested initial gene rating: Green; Evidence for inclusion: none provided; Evidence for exclusion: none provided; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none provided.

Created: 9 Sep 2019, 3:38 p.m. | Last Modified: 9 Sep 2019, 3:38 p.m.

Panel Version: 0.14